New Optical Technique for Rapid Malaria Diagnosis

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Secondary Speckle Sensing Microscopy (S3M)

Secondary Speckle Sensing Microscopy (S3M). The difference between an infected red blood cell (top) and a healthy cell (bottom) is revealed by S3M, in part, by considering the dynamics of the correlation value (CV). CV indicates the similarity between two patterns. 1,000 CVs are calculated from pairs of consecutive speckles acquired in 1 second. As shown in the chart at right, the CV oscillation range for the infected cell (top, 0.36) is almost three times larger than that of the healthy red blood cell (bottom, 0.13). In the top left image of the infected cell a parasitic life-cycle stage of malaria, called “trophozoite,” can be seen (arrow). Credit: Dan Cojoc, Materials Technology Institute, National Research Council, Italy.

Correctly and quickly diagnosing malaria is essential for effective and life-saving treatment. But rapid detection, particularly in remote areas, is not always possible because current methods are time-consuming and require precise instrumentation and highly skilled microscopic analysis.

Now, a promising new optical imaging system, described in a paper published today in the Optical Society’s (OSA) open-access journal Biomedical Optics Express, may make the diagnosis of this deadly disease much easier, faster, and more accurate. [Read more…]

Drug-Resistant Malaria Threatens Effort to Control Disease

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A team of researchers from the United States and Thailand says the growing number of cases of drug-resistant malaria being reported in Thailand and neighboring countries threatens the worldwide campaign to control and eliminate the mosquito-borne disease. The malaria parasite in the region is becoming resistant to the first-line malaria therapy – artemisinin combination treatment – and experts say there is a real danger of the resistant strain moving to Africa, where malaria is widespread.

“The biggest fear is the resistance will spread across Southeast Asia and then spill over into Africa, where the vast majority of the 700,000 deaths a year [from malaria] occur. Historically, we have seen that when resistance to chloroquine [another anti-malaria drug] spread, there was an increase in mortality due to malaria. This is a very, very urgent situation,” said Tim Anderson, of the Texas Biomedical Research Institute, who spoke to us via Skype.

Anderson was part of the team that found evidence of growing resistance to artemesinin therapy for malaria in the border regions of Thailand and Burma, which they fear can spread westward across south east Asia and into Africa. The researchers are calling for immediate steps to control the spread of the resistant malaria parasite.

The number of malaria deaths dropped in the last few years because of the artemisinin combination treatment, and Anderson predicts that mortality figures will rebound if the drug loses its efficacy.

“We are seeing that the drug kills the parasite 100-fold less well than it used to. That doesn’t mean that the parasites are not killed, so we can still cure patients. But the concern is that the number of patients who are NOT cured will rise. We currently estimate that about 30 percent of the patients are not cured with artemisinin,” said Anderson.

“I have to say that I am not actually all that surprised. Every time we have developed a new drug, the parasite has figured out a way to get around it,” said Dr. David Kaslow, the director of the PATH Malaria Vaccine Initiative – an international nonprofit organization committed to developing a malaria vaccine.

“The good news is that the first-ever malaria vaccine is on the horizon,” said Kaslow.

The malaria vaccine could be available by 2015, Kaslow said. But it will be just one more weapon against malaria, and the problem of resistance to artemisinin is real.

“It is a piece of a larger control and – hopefully, some day – elimination and eradication program. We have to use a variety of tools – [including] bed nets, indoor residual spraying, and preventive therapy,” said Kaslow.

Experts say drug-resistant strains of malaria likely will continue to emerge. The solution, they believe, is to support the development of new drugs and new therapies to fight the disease.

Source: VOA News

Resistance to Malaria Treatments Seriously Compromises Efforts to Eliminate Malaria

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Scientists have found new evidence that resistance to the front-line treatments for malaria is increasing.

They have confirmed that resistant strains of the malaria parasite on the border between Thailand and Burma, 500 miles (800km) away from previous sites.

Researchers say that the rise of resistance means the effort to eliminate malaria is "seriously compromised".

The details have been published in The Lancet medical journal.

[Read more…]

GM Mosquito Factory: Can Oxitec Mosquitoes Help Stamp Out Malaria?

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In plastic and glass containers thousands of mosquitoes are hatching in a British “mosquito factory.” On strips of brown paper there are hundreds of thousands of little black mosquito eggs.

“Here we practice birth control for mosquitoes,” says Hadyn Parry, CEO of Oxitec, a British bio-research company that makes genetically modified mosquito eggs. The eggs produce sterile male mosquitoes, incapable of fertilizing the females. [Read more…]

Treatment Outcome of Intravenous Artesunate in Patients with Severe Malaria in the Netherlands and Belgium

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Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe. [Read more…]

Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. Vivax

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Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).

Methods and Findings

In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.

Conclusions

IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.

Trial registration

ClinicalTrials.gov NCT00285662

Please see later full article for the Editors’ Summary (link below).

Citation: Senn N, Rarau P, Stanisic DI, Robinson L, Barnadas C, et al. (2012) Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial. PLoS Med 9(3): e1001195. doi:10.1371/journal.pmed.1001195

Academic Editor: Sanjeev Krishna, St George’s Hospital Medical School, United Kingdom

Received: July 5, 2011; Accepted: February 9, 2012; Published: March 27, 2012

Funding: This work was supported by a grant to the PNG Institute of Medical Research from the Bill & Melinda Gates Foundation’s Global Health Program (Grand ID# 34678). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.

Competing interests: SJR is a member of the PLoS Medicine Editorial Board. The authors have declared that no competing interests exist.

Abbreviations: AE, adverse event; AQ, amodiaquine; AS, artesunate; ATP, according to protocol; EPI, Expanded Programme on Immunization; Hb, hemoglobin; IPT, intermittent preventive treatment; IPTi, intermittent preventive treatment in infants; IRR, incidence rate ratio; LDR-FMA, ligase detection reaction/fluorescent microsphere assay; mITT, modified intention to treat; PE, protective efficacy; Pf, Plasmodium falciparum ; PNG, Papua New Guinea; Pv, Plasmodium vivax ; PYAR, person-year at risk; SAE, serious adverse event; SP, sulfadoxine-pyrimethamine

Authors: Nicolas Senn1,2,3,4#, Patricia Rarau1#, Danielle I. Stanisic1,5, Leanne Robinson1,5, Céline Barnadas1,5, Doris Manong1, Mary Salib1, Jonah Iga1, Nandao Tarongka1, Serej Ley1, Anna Rosanas-Urgell1, John J. Aponte6, Peter A. Zimmerman7, James G. Beeson5,8, Louis Schofield5, Peter Siba1, Stephen J. Rogerson2, John C. Reeder8, Ivo Mueller1,5,6*

1 Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea, 2 Department of Medicine, University of Melbourne, Melbourne Australia, 3 Swiss Tropical and Public Health Institute, Basel, Switzerland, 4 University of Basel, Basel, Switzerland, 5 Infection and Immunity Division, Walter and Eliza Hall Institute, Melbourne, Australia, 6 Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain, 7 Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, United States of America, 8 Burnet Institute, Melbourne, Australia

Full Article:Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial (PDF)

Source: PLOS Medicine

Copyright: © 2012 Senn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Breeding Site Characterization of Anopheles Sinensis Larvae in Chinese Villages

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Characterizing the breeding site of Anopheles sinensis is of major importance for the transition from malaria control to elimination in China. However, little information is available especially regarding the characteristics and influencing factors of breeding sites of An. sinensis in Yongcheng City, a representative region of unstable malaria transmission in the Huang-Huai River region of central China.

The aims of this study were to determine the breeding site characteristics of An. sinensis and related environmental and physicochemical parameters, to find out which breeding site characteristics could best explain the presence of An. sinensis larvae, and to determine whether the breeding habit of An. sinensis has changed or not.

Methods

Random repeated cross sectional study was undertaken in six villages of the Yongcheng city characterized by different levels of the historical incidence of P. vivax malaria. The potential breeding sites of An. sinensis larvae in each village were examined twice per month both in the household courtyards and the village surroundings. The larval sampling was done by the standard dipping method. Some important breeding site characterizations were recorded and characterized. The anopheline mosquito larvae and emerged adults were identified to the species level morphologically and to sub-species by the ribosomal DNA PCR technique. Chi-square analysis and logistic regression analysis were applied to determine the importance of factors for explaining the presence or absence of An. sinensis larvae.

Results

According to the ribosomal DNA PCR assay, all sampled anopheline mosquito larvae and emerged adults belonged to An. sinensis. Only 3 containers that were sampled from the household courtyards were found to contain An. sinensis larvae. There were no differences in the species composition of mosquito larvae among containers that contained water in the household courtyards (P > 0.05). An. sinensis larvae were shown to be present in a total of 60 breeding sites in the village surroundings, this included 8 (13.3%) river fringes, 26 (43.3%) ponds, 23 (38.3%) puddles, and 3 (5.0%) irrigation/drainage ditches. Logistic regression analysis revealed that the breeding site type, water depth, chemical oxygen demand (COD), ammonia nitrogen, and sulphate were found to be the key factors determining the presence of An. sinensis larvae. Approximately 94.9% of An. sinensis larvae inhabited relatively large and medium-sized water bodies, with depths between 0.5 m and 1.0 m (73.3%), COD lower than 2 mg/L (75%), ammonia nitrogen lower than 0.4 mg/L (86.7%), and sulphate lower than 150 mg/L (58.3%), respectively.

Conclusion

These results indicate that the majority of An. sinensis larval breeding sites were relatively large and medium-sized water bodies with depths between 0.5 m and 1.0 m, and containing low levels of COD, ammonia nitrogen, and sulphate, respectively. For effective An. sinensis larval control, the type of breeding site, water depth, COD, ammonia nitrogen, and sulphate should be given higher priority over other factors in areas where it is the primary vector.

Authors: Xiao-Bo Liu, Qi-Yong Liu, Yu-Hong Guo, Jing-Yi Jiang, Dong-Sheng Ren, Guang-Chao Zhou, Can-Jun Zheng, Jing-Li Liu, Yun Chen, Hong-Sheng Li, Hua-Zhong Li and Qun Li

Full Article: Random repeated cross sectional study on breeding site characterization of Anopheles sinensis larvae in distinct villages of Yongcheng City, People’s Republic of China (PDF)

Source: Parasites & Vectors 2012, 5:58 doi:10.1186/1756-3305-5-58

Published: 23 March 2012

Copyright: © 2012 Xiao-Bo Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Insecticide Susceptibility Status of Phlebotomus (Paraphlebotomus) Sergenti and Phlebotomus (Phlebotomus) Papatasi in Endemic Foci of Cutaneous Leishmaniasis in Morocco

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In Morocco, cutaneous leishmaniasis is transmitted by Phlebotomus sergenti and Ph. papatasi. Vector control is mainly based on environmental management but indoor residual spraying with synthetic pyrethroids is applied in many foci of Leishmania tropica. However, the levels and distribution of sandfly susceptibility to insecticides currently used has not been studied yet. Hence, this study was undertaken to establish the susceptibility status of Ph. sergenti and Ph. papatasi to lambdacyhalothrin, DDT and malathion.

Methods

The insecticide susceptibility status of Ph. sergenti and Ph. papatasi was assessed during 2011, following the standard WHO technique based on discriminating dosage. A series of twenty-five susceptibility tests were carried out on wild populations of Ph. sergenti and Ph. papatasi collected by CDC light traps from seven villages in six different provinces. Knockdown rates (KDT) were noted at 5 min intervals during the exposure to DDT and to lambdacyhalothrin. After one hour of exposure, sandflies were transferred to the observation tubes for 24 hours. After this period, mortality rate was calculated. Data were analyzed by Probit analysis program to determine the knockdown time 50% and 90% (KDT50 and KDT90) values.

Results

Study results showed that Ph.sergenti and Ph. papatasi were susceptible to all insecticides tested. Comparison of KDT values showed a clear difference between the insecticide knock-down effect in studied villages. This effect was lower in areas subject to high selective public health insecticide pressure in the framework of malaria or leishmaniasis control.

Conclusion

Phlebotomus sergenti and Ph. papatasi are susceptible to the insecticides tested in the seven studied villages but they showed a low knockdown effect in Azilal, Chichaoua and Settat. Therefore, a study of insecticide susceptibility of these vectors in other foci of leishmaniasis is recommended and the level of their susceptibility should be regularly monitored.

Authors: Chafika Faraj, Souad Ouahabi, El Bachir Adlaoui, Mohamed Elkohli, Lhoussine Lakraa, Mohammed ElRhazi and Btissam Ameur

Full Article: Insecticide susceptibility status of Phlebotomus (Paraphlebotomus) sergenti and Phlebotomus (Phlebotomus) papatasi in endemic foci of cutaneous leishmaniasis in Morocco (PDF)

Source: Parasites & Vectors 2012, 5:51 doi:10.1186/1756-3305-5-51

Published: 19 March 2012

Copyright: © 2012 Chafika Faraj et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Malaria Life Cycle

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The three parts of the malaria life cycle are known as the exo-erythrocytic cycle, the erythrocytic cycle and the sporogonic cycle. The first two of these take place in the human (or other mammal) host, while the third occurs in the mosquito vector.

Simulations Plus Announces Preliminary Success in Malaria Drug Design Project

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Simulations Plus, Inc., a provider of consulting services and software for pharmaceutical discovery and development, today announced that preliminary testing shows that one of the molecules it has designed to inhibit the malaria parasite has been shown to be a potent inhibitor of the malaria parasite.

Dr. Robert Clark, director of life sciences for Simulations Plus, said: “We’re excited to announce that, as a result of initial testing of five of the compounds we designed to inhibit the Plasmodium falciparum malaria parasite, four of the five showed some inhibition of the parasite, and one of those four showed very potent inhibition at a level suitable to be a therapeutic agent. Of course, inhibiting the parasite does not necessarily mean that this molecule would be a good drug. There are many more properties that must be acceptable and years of development needed before that could happen. But this is a remarkable achievement nonetheless, because it demonstrates that using only predictions and design methods from our MedChem Studio(TM), MedChem Designer(TM), ADMET Predictor(TM), and GastroPlus(TM) software and some public domain data, we were able to design completely new chemical structures that can hit a target. There remain a few more molecules in synthesis, and those will be tested once synthesis and purification have been completed by our synthesis company, Kalexsyn, Inc., of Kalamazoo, MI. Among those molecules are the ones we believed would be the most potent inhibitors of the malaria parasite. They are a bit more difficult to synthesize, but Kalexsyn indicates that they are well along in the process and expect to complete the final steps very soon.”

Dr. Michael Lawless, team leader for cheminformatics studies for Simulations Plus, added: “The first round of tests was against the drug-sensitive strain of the malaria parasite known as 3D7. The next round will be against the drug-resistant strain — a more important measure of the potential usefulness of these new molecular structures. We hope to have results by the end of the month from those experiments. We’re shipping samples of the first five molecules to a company that will perform a series of experiments to measure a few other properties, including some physicochemical and metabolism properties. Those experiments will tell us if our predictions for some important ADME (Absorption, Distribution, Metabolism, and Excretion) properties were on the mark.”

 

Source: Business Wire